This invention relates to a chemical and/or biological analysis device equipped with an analysis support that may be of the single use type.
The invention is used in applications in chemistry and biology. In particular, the device may be used in chemical amplification processes or PCR (Polymerase Chain Reaction) type processes for the analysis of genetic material (DNA).
Macroscopic chemical or biological analysis systems using titration plates are known. These plates comprise bowls in which samples and reagents are mixed by pipetting (with a pipette). The plates are heated to set temperatures by successive oven drying, and are then cooled, in order to enable the chemical or biological reactions.
With these systems, the addition of reagents is a long and complex operation, particularly because each reagent is added separately in turn. Furthermore, the thermal inertia involved in heating and cooling of the titration plates is too high, increasing the analysis time.
Furthermore, chemical and/or biochemical analysis equipment is known in the form of complete structures incorporating heating means necessary for analysis. Connection systems with pipes are used to input the samples and reagents into the structure.
The use of this equipment requires complex and tedious connection operations to input the fluids, analytes and reagents, and electrical connection operations to supply power to the heating equipment. Due to the specific nature of the analyses, connection operations have to be repeated every time that the equipment is used.
Furthermore, the manufacturing cost of this equipment is high.
A more complete illustration of the techniques and equipment used for biochemical analysis purposes is given in documents (1) and (2), the references of which are given at the end of this description.
The purpose of the invention is to propose a biological and/or chemical analysis device without the limitations mentioned above.
Another purpose is to reduce heating and cooling times, and to enable a precise and selective temperature check of components to be analysed during different reaction phases.
Another purpose of the invention is to propose such a device that can quickly be adapted to different types of products to be analysed without requiring any complex connection operations.
Another purpose of the invention is to propose a single-use, very lost cost device with an analysis support, that can be thrown away and replaced after each use, or after a limited number of uses. For example, it might be possible to perform about a thousand sequential analyses with a device before throwing it away.
In order to achieve these purposes, the objective of the invention is more precisely a chemical and/or biological analysis device comprising an analysis support with at least one input bowl to collect a sample, at least one output bowl through which the said sample is returned, at least one internal duct passing through the support to connect the input bowl to the output bowl, and at least one reagent reservoir connected to each duct between an input bowl and an output bowl, in which the input bowl, the output bowl and the reservoir open up onto a first face of the analysis support.
In particular, the device may comprise several input bowls and several corresponding output bowls, each input bowl being connected to an associated output bowl through a duct.
Liquids to be analysed may be put into the input bowls and/or reagents may be put into the corresponding reservoirs by micropipetting (using a micropipette).
According to another embodiment, liquids to be analysed may be placed into the input bowls and/or the reagents may be put into the corresponding reservoirs using leak tight fluids input devices such as a lid placed on the reservoir or the bowl and connected to a syringe or a pressurized tank.
Liquids and/or reagents may be placed using a combination of the two methods described above.
For supports with a large number of bowls and/or reservoirs, the liquids to be analysed and/or the reagents may be brought in automatically by means of a high-resolution distribution (dispensing) robot. Furthermore, sequential analyses in which at least one of the reagents is replaced by another over a period may be automated by sequentially adding several different reagents into the corresponding reservoir. A neutral buffer liquid may or may not be added into the reservoir between two distinct reagents.
According to one particular aspect of the invention, the internal duct(s) may be designed to be brought close to at least a second face of the analysis support so that there is only a thin wall separating it from the said second face. In one particular embodiment, the thin wall may be less than 100 xcexcm thick.
More precisely, the wall is chosen to be sufficiently thin to enable heat exchange with thermal sources external to the analysis support.
In particular, the wall separating the ducts from the second face may be chosen to be thinner than a wall separating ducts from each other or from the bowls.
According to another aspect of the invention, the face of the ducts opposite the thin wall may have a thermal barrier that can be made using a layer of material that does not conduct heat well and/or a substrate structure in which a cavity filled with air or a gas that is not a good heat transporter can be located on the ducts.
This thermal barrier can make the temperature in the ducts more uniform.
According to another aspect of the invention, the device may also comprise a thermal support independent of the analysis support, the thermal support comprising a heat exchange face with at least one thermal source and the said thermal support possibly being added removably onto the analysis support in order to bring the heat exchange face into contact with the second face of the analysis support.
The separate nature of the analysis support and the thermal support makes it possible to design analysis supports without their own heating or cooling means. Consequently, this characteristic can significantly reduce the cost of the analysis support. Thus, this support may be of the single use type or it may be used several times, in other words it may be thrown away after one or several uses. One use means the sequential production of a number of analyses, for example close to 1000.
The heat exchange face may comprise one or several thermostat controlled areas each equipped with at least one thermal source. The thermostat-controlled areas coincide with at least one analysis support area located on the downstream side of a connector between a reagent reservoir and a duct.
By associating a thermostat controlled area of the thermal support with a corresponding area of the analysis support located nearby, for example on the downstream side of each reagent reservoir, it would be possible to control and selectively adapt the temperature of the liquid to be analysed as a function of each reagent used.
The term downstream side used in this case is applicable to the direction of flow of liquids to be analysed starting from the input bowls and working towards the output bowls.
Thermal sources may comprise one or several thermostat controlled electric heating resistances.
Alternately, or additionally, the thermal sources may also comprise one or several ducts through which a heat transporting fluid passes. This fluid may be used to locally heat or cool the analysis support.
In one particular embodiment of the analysis support, it may be provided with a first substrate with transverse openings that form the bowls and reservoirs respectively, and a second substrate glued to the first substrate, the second substrate being provided with grooves covered by the first substrate to form ducts, and coinciding with the corresponding through openings.
This particularly simple structure can reduce manufacturing costs of the analysis supports.
The support may be manufactured according to the invention using a process comprising the following steps in sequence:
formation of through openings in a first substrate, the said openings corresponding to an input or output bowl, or a reagent reservoir,
formation of grooves in a second substrate, according to a pattern that joins at least two openings in the first substrate to each other,
gluing of the first substrate onto the second substrate in order to cover the grooves,
thinning of the second substrate after gluing, maintaining a thickness of the substrate greater than the maximum depth of the grooves.
According to one particular embodiment, the first substrate may be provided with two layers that are not good conductors of heat, for example a few microns thick.
According to a second particular embodiment, the first substrate may comprise at least one non-through opening in order to create at least one thermal insulation cavity.
The invention also relates to a process for use of the analysis device as described above, in which the analysis support is put into contact with the thermal support for a determined analysis time, at least one sample to be analysed and at least one reagent being added into the analysis support before the analysis phase starts, or during the analysis phase, and then the analysis support is removed from the thermal support after the analysis phase.
The analysis support may be reused after the end of the analysis.